Like Rory Deutsch, most of the children diagnosed with the deadly brain tumor known as a brain stem glioma hardly have a chance. Brain stem gliomas infiltrate the area of the brain that houses centers for cranial nerves that control the movement and sensation of the throat, tongue, eyes and face and is the center for breathing, heartbeat and consciousness. Malignant 95 percent of the time, this type of tumor typically snuffs out the life of a child in 9 to 12 months. Less than 5 percent of children diagnosed with a brain stem glioma are alive in 2 years.

"What makes a brain stem glioma so deadly is its location. Just taking a biopsy of the tumor could irreparably damage a child neurologically," says neurosurgeon Tadanori Tomita, MD, director of Children's Brain Tumor Center. "Tumors located on two of the three portions of the brain stem can be removed because they are often benign. However, surgery within the center of the brain stem is too much of a risk to the child, and these tumors are almost always malignant.

Inoperable because of their location, brain stem gliomas also are resistant to most currently available chemotherapy and radiation therapies. Conventional radiation therapy usually can prolong the life of an affected child by months, while traditional delivery of chemotherapy, even in high doses, doesn't appear to be a good way to effectively cure or treat a brain stem tumor. In addition, high doses of chemotherapy drugs can have serious side effects.

Neuro-oncologist Stewart Goldman, MD, who co- directs the Brain Tumor Center with Dr. Tomita, says, "We're here to treat children, not just their tumors. When we design therapies, we can't just think about killing the cancer cells; we have to think about what it does to the child. For example, the amount of radiation needed to kill a brain tumor will destroy the child's normal brain function. So, we have to look for new approaches."

Drs. Tomita and Goldman, joined by Dr. Mary Ann Marymount, director of pediatric radiation oncology at Children's, and her associate Dr. John Kalapurakal, are doing just that. The following are a few examples of research being proposed and performed:

• Interstitial therapy – Most current chemotherapy involves an intravenous route for the anti-cancer which is circulated throughout the entire body. Consequently, the entire body is exposed to the chemotherapy and its potential side effects. An alternate method is to inject the medicine directly into the artery that leads to the brain stem and the tumor. An even more appealing solution would be to put the chemotherapy that kills cancer cells directly into the tumor. By improved surgical techniques using stereotactic measures (using a CT/MRI scan and a frame on the patient's head to make a three-dimensional measurement) doctors can obtain information that helps them know exactly how deep and in what place to put the small needle into a tumor and inject the medicine directly.

• New types of Agents – Investigation is underway on how cells get energy from the blood supply. As tumors grow they need to develop their own blood supply (angiogenesis). Current research on angiogenesis with the compound thrombosponden is being conducted at Northwestern University. Anti-angiogenic agents (compounds that block new blood vessel formation, thus starving tumors) are under current investigation as a means to stop tumor growth. The drug Thalidomide also has proven to be an anti-angiogenic, and investigations are underway at Children's to see if it would be effective in treating brain tumors. Every cell in the body needs energy to grow; the brain uses glucose as its energy source. The diagnostic test, the PET scan, shows where glucose is used and makes it traceable. A special kind of glucose known as 2-flouro-deoxyglucose has been found to protect normal brain cells from radiation, while also making tumor cells more susceptible to treatment because it "blocks" their glucose metabolism. Research based on adult and animal models is expected to show exactly how this can be accomplished.

• Radiation therapy – Radiation therapies can stop tumor growth and make it smaller for a while, but new approaches are needed to make radiation work better. Radiation oncologists are investigating the possibility of giving higher doses of radiation, again by stereotactic measures, but splitting it into small fractions at different times of the day.

• Basic science research – Translational research, or basic science research that can be applied to the bedside, is another area of investigation. Exploring how growth factors affect tumors, researchers are looking for ways to impede or stop this growth completely, and this may have applications in treating brain stem gliomas. Dr. Eric Bremer of Children's Memorial Institute for Education and Research (CMIER) is currently investigating what turns tumor cells on and off. Some of this work may have applications down the road for brain stem glioma treatment.

Clearly more research is needed to find better treatments for brain stem gliomas and other deadly brain tumors. Support for research has been lacking because the number of children affected are relatively small; of the 1,500-2,000 brain tumors diagnosed in children each year, brain stem gliomas account for 8 to 10 percent. Even so, hope for youngsters with this condition is being promoted through some very dedicated sources. The Rory David Deutsch Foundation was recently established by the parents of Rory David Deutsch, who died of a brain stem glioma last year. Funds from the foundation are earmarked specifically for research into the cause and treatments of brain stem gliomas. On April 25th, the foundation held its inaugural event "Soar to the Stars for Rory!" at the Adler Planetarium. At that time the foundation made a $250,000 gift to Children's for brain stem glioma research.

"Even if we see the survival rate nudged up by only 20 or 30 percent in my lifetime, it would be a great accomplishment," says Dr. Goldman. "It's our ambition to make that change in prognosis happen for these kids."